Enhanced spinal cord injury repair by nerve extracellular matrix/carboxymethyl chitosan /oxidized alginate hydrogel containing OE-MSCs.

Hydrogels containing stem cells are a promising strategy to improve spinal cord injury (SCI) repair. Recent advances in tissue engineering have made cell-containing hydrogels more effective for achieving better regeneration outcomes. One such advancement is the incorporation of decellularized extracellular matrix (ECM) into hydrogels to develop a cell-compatible environment that mimics the mechanical and biological properties of native tissue ECM. Herein, a unique bioactive injectable hydrogel based on decellularized nerve ECM, carboxymethyl chitosan (CMC) and oxidized alginate (OA) was fabricated and characterized. After confirming the physicochemical properties as well as cytocompatibility of the hydrogel, olfactory-derived ectomesenchymal stem cells (OE-MSCs) were selected for encapsulation within the hydrogel due to their capacity to secrete neurotrophic and anti-inflammatory factors that support axonal regeneration and remyelination. In vivo study, injection of the hydrogel containing OE-MSCs into SCI models was able to effectively fill cystic cavities at the lesion site and provide a suitable microenvironment to promote axonal regeneration and remyelination. These findings resulted in significant functional recovery in the hydrogel/cell group compared to the other groups. Overall, this study highlights the potential of bioactive injectable hydrogel based on nerve ECM, CMC and OA combined with OE-MSCs to enhance SCI regeneration.